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Serum Ghrelin Levels in Acromegaly: Effects of Surgical and Long-Acting Octreotide Therapy

Department of Medicine, Columbia College of Physicians and Surgeons, New York, New York 10032

Address all correspondence and requests for reprints to: Pamela U. Freda, M.D., Department of Medicine, Columbia College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032. E-mail: puf1{at}columbia.edu.

The orexigenic peptide, ghrelin, is regulated by acute and chronic nutritional state. Although exogenously administered ghrelin stimulates pituitary GH secretion, little is known about the role of ghrelin in endogenous GH secretion or how high GH and IGF-I levels in acromegaly could affect ghrelin secretion and vice versa. Therefore, we evaluated fasting and post oral glucose tolerance test serum ghrelin levels in 19 patients with active acromegaly at baseline and after either surgery in 9 of these or administration of long-acting octreotide (Sandostatin LAR) in the other 10 patients. After surgical cure, fasting ghrelin rose from 312 ± 56 pg/ml to 548 ± 97 pg/ml (P = 0.013). Fasting serum ghrelin levels were higher in all patients after surgery and ranged between 112% and 349% of presurgery levels. Ghrelin levels fell significantly during long-acting octreotide therapy from 447 ± 34 pg/ml to 206 ± 15 pg/ml (P < 0.0001); ghrelin levels on octreotide ranged between 26% and 70% of baseline levels. Serum ghrelin levels were suppressed significantly during the oral glucose tolerance test in both groups. Pretherapy ghrelin levels correlated negatively with serum insulin levels (r = -0.494; P = 0.03) and insulin resistance as estimated by the homeostasis model assessment score (r = -0.573; P = 0.01). In patients without diabetes mellitus, serum insulin levels in the surgical group were 19.7 ± 5.4 µU/ml before surgery and fell to 9.7 ± 0.93 µU/ml after surgery (P = 0.05); levels in the octreotide group were 13.9 ± 2.8 µU/ml before and fell to 11.2 ± 2.8 µU/ml on octreotide (P = 0.03). Pretherapy ghrelin levels did not correlate with weight or body mass index, but after therapy in the surgery group ghrelin correlated negatively with weight (r = -0.823, P = 0.012) as has been demonstrated by others in healthy subjects. Ghrelin secretion is dysregulated in active acromegaly; lowered serum levels of ghrelin in active acromegaly rise along with the postsurgery normalization of GH and IGF-I and improved insulin resistance. In contrast to surgical therapy, long-acting octreotide therapy persistently suppressed serum ghrelin levels. It remains to be determined whether altered circulating ghrelin concentrations could impact on body composition changes in acromegaly.

This work was supported by National Institutes of Health Grants DK02561 and DK60475 (to P.U.F.) and DK57561 (to S.L.W.).

Abbreviations: BMI, Body mass index; CV, coefficient of variation; GI, gastrointestinal; HOMA, homeostasis model assessment; IRMA, immunoradiometric assay; OGTT, oral glucose tolerance testing.

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